An open label study followed by a randomised, double-blind, placebo-controlled, parallel group and an extension study to investigate the safety and efficacy of GB1211 (a galectin-3 inhibitor) in combination with atezolizumab in patients with Non-Small Cell Lung Cancer (NSCLC).
试验速览
- 阶段
- 2 期
- 状态
- 招募中
- 入组人数
- 49
- 试验地点
- 7
- 主要终点
- Part A: number of AEs in the 200 mg group compared to number of AEs in the dosing group (s).
研究概览
简要总结
Part A: To assess the safety and tolerability of GB1211 200 mg and other doses established during the study, administrated BID in combination with atezolizumab. Part B: To assess the safety and tolerability of GB1211 in the recommended dose in combination with atezolizumab compared to atezolizumab and placebo in patients with NSCLC, on a double blind, randomized fashion. To assess the efficacy of GB1211 compared to placebo by measuring the change of the longest diameters of target lesions at week 12 in NSCLC patients who are receiving atezolizumab. Part C: To assess the long-term safety and tolerability of GB1211 in combination with atezolizumab compared to atezolizumab alone.
入排标准
- 年龄范围
- 18 years 至 65+ years（18-64 Years, 65+ Years）
- 接受健康志愿者
- 是
入选标准
- •Must be ≥ 18 years of age at the time of signing the Informed Consent Form (ICF).
- •Diagnosed NSCLC stage IIIB that either progressed after curative therapy (chemoradiation and/or surgery) or is not candidate to curative therapy, or Stage IV metastatic disease (de novo or distant relapse) [According to UICC TNM edition 8].
- •Measurable disease, as defined by RECIST v1.
- •Expressing PD-L1 on at least 50% of tumour cells (PD-L1 stained ≥ 50% of tumour cells [TC ≥ 50%] or PD-L1 stained tumour-infiltrating immune cells [IC] covering ≥ 10% of the tumour area [IC ≥ 10%]), as determined through use of the Dako PD-L1 IHC 22C3 pharmDx assay or the Ventana PD-L1 IHC SP263 assay
- •Agree to have a tumour biopsy that is eligible for Gal-3 expression evaluation before the first study drug dose.
- •Patients receiving therapeutic anticoagulation must be on stable regimen.
- •Adequate haematologic and end-organ function, defined by the following laboratory test results, obtained within 14 days prior to initiation of study treatment: • Absolute neutrophil count (ANC) ≥ 1.5 × 109/L (1500/μL) without granulocyte colony-stimulating factor support. • Lymphocyte count ≥ 0.5 × 109/L (500/μL). • Platelet count ≥ 100 × 109/L (100,000/μL) without transfusion. • Haemoglobin ≥ 90 g/L (9 g/dL). Patients may be transfused to meet this criterion. • Aspartate aminotransferase (AST), alanine aminotransferase (ALT), and alkaline phosphatase (ALP) ≤ 2.5 × upper limit of normal (ULN), with the following exceptions: o Patients with documented liver metastases: AST and ALT ≤ 5 × ULN. o Patients with documented liver or bone metastases: ALP ≤ 5 × ULN. • Total bilirubin ≤ 1.5 × ULN with the following exception: Patients with known Gilbert disease: total bilirubin ≤ 3 × ULN. • Creatinine clearance ≥ 50 mL/min (calculated using the CockcroftGault formula). • Albumin ≥ 25 g/L (2.5 g/dL). • For patients not receiving therapeutic anticoagulation: INR and a PTT ≤ 1.5 × ULN.
- •Eastern Cooperative Oncology Group (ECOG) performance status of 0 to
- •Have not received prior systemic chemotherapy for the treatment of recurrent, advanced or metastatic disease, treatment with chemotherapy and/or radiation as part of neoadjuvant/adjuvant therapy is allowed as long as completed at least 4 weeks prior to diagnosis of recurrent advanced or metastatic disease
- •Patients must not have received immune checkpoint inhibitors previously.
- •Must be eligible for atezolizumab at 1200 mg every 3 weeks as defined in the atezolizumab product label
- •Must provide signed ICF.
- •Must have the ability to comply with the study protocol, in the investigator's judgment.
- •Women of childbearing potential must agree to remain abstinent (refrain from heterosexual intercourse) or use contraceptive measures and agree to refrain from donating eggs.
- •Men must agree to remain abstinent (refrain from heterosexual intercourse) or use contraceptive measures and agree to refrain from donating sperm.
排除标准
- •Patients with known hypersensitivity to GB1211 or any of the excipients.
- •Patients with a history of arrhythmia, especially ventricular arrhythmias, atrial fibrillation or recent recovery of rhythm after atrial fibrillation.
- •Patients with bradycardia (<50 beats per minute).
- •Patients with left ventricular ejection fraction (LVEF) of ≤40% assessed according to local clinical practice.
- •Patients with a family history of sudden cardiac death before the age of
- •Patients with a QT/QTc interval > 470 ms (for women) and > 450 ms (for men) at screening or congenital long QT syndrome.
- •Patients with history of organ transplant or hematopoietic stem cell transplantation.
- •Patients who have received GB1211 prior to this study
- •Major surgery within 3 weeks before the study
- •Treatment with systemic immunostimulatory agents (including, but not limited to, interferon and interleukin 2 [IL-2]) within 4 weeks or 5 drug-elimination half-lives (whichever is longer) prior to initiation of study treatment.
- •Treatment with systemic immunosuppressive medication (including, but not limited to, corticosteroids, cyclophosphamide, azathioprine, methotrexate, thalidomide, and anti-tumour necrosis factor-a [TNF-a] agents) within 2 weeks prior to initiation of study treatment, or anticipation of need for systemic immunosuppressive medication during study treatment.
- •Life expectancy ≤ 12 weeks from the expected start of study treatment date
- •Active or history of autoimmune disease or immune deficiency, including, but not limited to, myasthenia gravis, myositis, autoimmune hepatitis, systemic lupus erythematosus, rheumatoid arthritis, inflammatory bowel disease, anti-phospholipid antibody syndrome, Wegener granulomatosis, Sjögren syndrome, Guillain-Barré syndrome, or multiple sclerosis.
- •Patients with acute neurological events (e.g., intracranial or subarachnoid haemorrhage, stroke, intracranial trauma) within 6 months of inclusion
- •Patients with symptomatic, untreated, or actively progressing central nervous system (CNS) metastases confirmed by a CT or MRI scan.
- •History of malignancy other than NSCLC within 2 years prior to screening, with the exception of malignancies with a negligible risk of metastasis or death (e.g., 5-year OS rate ≥ 90%), such as adequately treated carcinoma in situ of the cervix, nonmelanoma skin carcinoma, localized prostate cancer, ductal carcinoma in situ, or Stage I uterine cancer
- •Patients with past medical history or any evidence of clinically active interstitial lung disease, including drug-induced interstitial lung disease.
- •Uncontrolled significant pleural effusion.
- •History of non-infectious pneumonitis that required steroids or current pneumonitis.
结局指标
主要结局
Part A: number of AEs in the 200 mg group compared to number of AEs in the dosing group (s).
Part A: number of AEs in the 200 mg group compared to number of AEs in the dosing group (s).
Part B: number of AEs with GB1211 and atezolizumab compared to placebo and atezolizumab. The incidence, frequency and severity of AEs, SAEs, treatment related AEs, immune-related AEs, Grade 3 and above AEs and AEs leading to GB1211 discontinuation or study withdrawal. The incidence and frequency of laboratory parameter abnormalities.
Part B: number of AEs with GB1211 and atezolizumab compared to placebo and atezolizumab. The incidence, frequency and severity of AEs, SAEs, treatment related AEs, immune-related AEs, Grade 3 and above AEs and AEs leading to GB1211 discontinuation or study withdrawal. The incidence and frequency of laboratory parameter abnormalities.
Part B: The percentage change from baseline in the sum of longest diameters of target lesions at Week 12, %ΔTSWk12, based on ICR according to RECIST 1.1.
Part B: The percentage change from baseline in the sum of longest diameters of target lesions at Week 12, %ΔTSWk12, based on ICR according to RECIST 1.1.
Part C: The number of AEs with GB1211 and atezolizumab compared to placebo and atezolizumab. The incidence, frequency and severity of AEs, SAEs, treatment related AEs, immune-related AEs, Grade 3 and above AEs and AEs leading to GB1211 discontinuation or study withdrawal.
Part C: The number of AEs with GB1211 and atezolizumab compared to placebo and atezolizumab. The incidence, frequency and severity of AEs, SAEs, treatment related AEs, immune-related AEs, Grade 3 and above AEs and AEs leading to GB1211 discontinuation or study withdrawal.
次要结局
- Part A: The recommended tolerable dose of GB1211 in combination with atezolizumab determined by assessment of SAEs, treatment related AEs, immune-related AEs, Grade 3 and above AEs and AEs leading to GB1211 discontinuation or study withdrawal in the sentinel groups.
- Part A and B: Clinical effects in accordance with RECIST v1.1: o ORR based on Local Tumour Assessment (LTA) (Part A) and ICR (Part B). o DoR and TTR. o TTP is defined as the time from randomisation until objective tumour progression. TTP does not include deaths. o Disease Control defined as patients with a response or stable disease, assessed at each imaging assessment from randomisation to progression or death due to any cause, whichever occurs first.
- Part A and B: Plasma concentrations of GB1211 and derived pharmacokinetic parameters including Cmax, Tmax, AUC and others, as appropriate.
- Part C: ORR (CR and PR), clinical benefit (CR, PR and SD), DoR and PFS. Time to PR or CR for those patients who enter the study with SD as best response. PFS is defined as the time from the first dose until the first documentation of disease progression or death due to any cause, whichever occurs first.
研究者
Hans Schambye
Scientific
Galecto Biotech AB